The main objective of the proposed work is to isolate and characterize the active constituents of diets containing culture filtrates of the mold Trichoderma viride, and some cereals, particularly barley, which have recently been found by us to suppress by up to 90% the biosynthesis of cholesterol in chicken liver. Specifically, we propose to investigate in detail the effect of dietary cereals, supplemented and without the T. viride products, on the activities of beta-hydroxy-beta-methylglytaryl-CoA (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase (the rate-limiting enzymes in the biosynthesis and degradation of cholesterol, respectively), fatty acid synthetase, acetyl-CoA carboxylase, lipogenic enzymes in liver and adipose tissues of chickens and rats. T. viride filtrates will be fractionated by conventional biochemical techniques prior to identification of the active compound(s) by nuclear magnetic resonance and mass spectrometry. Different barley types will be fractionated into several kernel components and examined for activity. Effective levels of the active principles in the diets of rats and chickens will be ascertained. The effect of these materials on cholesterol biosynthesis will ultimately be measured in isolated cell and cell-free systems from rat and chicken liver. The pronounced effects observed by us which are detailed in this proposal have implications for human nutrition and possible control of cardiovascular diseases in which cholesterol plays a key role.